恩格列凈作用機(jī)制 - Medchemexpress - MCE中國(guó)

1、Product Data SheetEmpagliflozinCat. No.: HY-15409CAS No.: 864070-44-0分式: CHClO分量: 450.91作靶點(diǎn): SGLT作通路: Membrane Transporter/Ion Channel儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 250 mg/mL (554.43 mM; Need ultrasonic)H2O : 0.11 mg/mL (0.24 mM; Need ultrasoni

2、c and warming)SolventMass1 mg 5 mg 10 mgConcentration制備儲(chǔ)備液1 mM 2.2177 mL 11.0887 mL 22.1774 mL5 mM 0.4435 mL 2.2177 mL 4.4355 mL10 mM 0.2218 mL 1.1089 mL 2.2177 mL請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲(chǔ)備液；旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?6 個(gè)內(nèi)使，-20C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?1 個(gè)內(nèi)使。體內(nèi)實(shí)驗(yàn)請(qǐng)根

3、據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥式選擇適當(dāng)?shù)娜芙獍?。以下溶解案都?qǐng)先按照 In Vitro 式配制澄清的儲(chǔ)備液，再依次添加助溶劑：為保證實(shí)驗(yàn)結(jié)果的可靠性，澄 的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使； 以下溶劑前顯的百分 指該溶劑在您配制終溶液中的體積占；如在配制過(guò)程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過(guò)加熱和/或超聲的式助溶1. 請(qǐng)依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.08 mg/mL (4.61 mM); Clear solution此案可獲得 2.08 mg/mL (4.61 mM，

4、飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 20.8 mg/mL 的澄 DMSO 儲(chǔ)備液加到 400 L PEG300 中，混合均勻；向上述體系中加50 L Tween-80，混合均勻；然后繼續(xù)加 450 L 理鹽定容 1 mL。2. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.08 mg/mL (4.61 mM); Clear solutionPage 1 of 2 www.MedChemE此案可獲得 2.08 mg/mL (4.61 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取

5、100 L 20.8 mg/mL 的澄 DMSO 儲(chǔ)備液加到 900 L 20% 的 SBE-CD 理鹽溶液中，混合均勻。3. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.08 mg/mL (4.61 mM); Clear solution此案可獲得 2.08 mg/mL (4.61 mM，飽和度未知) 的澄 溶液，此案不適于實(shí)驗(yàn)周 期在半個(gè)以上的實(shí)驗(yàn)。以 1 mL 作液為例，取 100 L 20.8 mg/mL 的澄 DMSO 儲(chǔ)備液加到 900 L 油中，混合均勻。BIOLOGICAL ACTIVITY物活性 Empagliflozin種選擇

6、性鈉葡萄糖協(xié)同轉(zhuǎn)運(yùn)蛋-2 (SGLT-2) 抑制劑，抑制SGLT-2的IC50 為3.1 nM。IC & Target IC50: 3.1 nM (SGLT-2), 1.1 M (SGLT-5), 2 M (SGLT-6), 8.3 M (SGLT-1), 11 M (SGLT-4)1體外研究 Empagliflozin is a potent and competitive SGLT-2 inhibitor with an excellent selectivity profile and the highestselectivity window of the tested SGLT-2

7、inhibitors over hSGLT-1. Empagliflozin inhibits the uptake of 14C-alpha-methyl glucopyranoside (AMG) via hSGLT-2 in a dose-dependent manner with an IC50 of 3.1 nM, but is less potent forother SGLTs (IC50 range: 1100-11000 nM). 3H-Empagliflozin displays a high affinity for SGLT-2 with a mean Kd of573

8、7 nM in the absence of glucose in kinetic binding experiments1.體內(nèi)研究 Glucose intolerance is significantly improved after 8 days of Empagliflozin treatment at either dose (3mg/kg Empagliflozin 3058180 vs 10mg/kg Empagliflozin 3090219). Therefore, acute treatment with Empagliflozin has a beneficial eff

9、ect on hyperglycemia and glucose intolerance. Since there are no significant differences in blood glucosehomeostasis with the two different doses of Empagliflozin, and random blood glucose levels of T1DM mice aresignificantly improved by 3mg/kg of Empagliflozin, the effect of the lower dose of Empag

10、liflozin (3mg/kg) isinvestigated on preserving -cell mass and function2.PROTOCOLAnimal Mice2Administration 2 Male C57BL/6J mice (10 weeks of age) are used. Empagliflozin is dissolved in hydroxy ethyl cellulose (HEC) andadministered to mice in the experimental group (3 or 10 mg/kg) by oral gavage onc

11、e daily for 8 days, whereas thevehicle group is given same volume of HEC alone.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Diabetologia. 2017 Mar;60(3):568-573. Cell Physiol Biochem. 2019 Nov. Biochem Pharmacol. 2018 Jun;152:45-59. Mol C

12、ell Endocrinol. 2019 Jun 10:110487. Life Sci. 2019 Jul 1:116622.See more customer validations on HYPERLINK www.MedChemE www.MedChemEPage 2 of 3 www.MedChemEREFERENCES1. Grempler R, et al. Empagliflozin, a novel selective sodium glucose cotransporter-2 (SGLT-2) inhibitor: characterisation and compari

13、son with other SGLT-2inhibitors. Diabetes Obes Metab. 2012 Jan;14(1):83-90.2. Cheng ST, et al. The Effects of Empagliflozin, an SGLT2 Inhibitor, on Pancreatic -Cell Mass and Glucose Homeostasis in Type 1 Diabetes. PLoS One. 2016Jan 25;11(1):e0147391.3. Nikole J.ByrneBSc, et al. Empagliflozin Prevent

14、s Worsening of Cardiac Function in an Experimental Model of Pressure Overload-Induced Heart Failure.JACC Basic Transl Sci. 2017 Aug;2(4):347-354.4. Sakaeda T, et al. Susceptibility to serious skin and subcutaneous tissue disorders and skin tissue distribution of sodium-dependent glucose co-transporter type 2 (SGLT2) inhibitors. Int J Med Sci. 2018 Jun 13;15(9):937-943.McePdfHe